Bruce Sachais, M.D./Ph.D.
Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations
Contact information
605A Stellar Chance
422 Curie Boulevard
University of Pennsylvania
Philadelphia, PA 19104
422 Curie Boulevard
University of Pennsylvania
Philadelphia, PA 19104
Office: 215 898-0568
Fax: 215 573-0252
Fax: 215 573-0252
Email:
sachais@mail.med.upenn.edu
sachais@mail.med.upenn.edu
Publications
Links
Search PubMed for articles
Research Description Video
Department of Pathology and Laboratory Medicine
Cell and Molecular Biology Graduate Group
Search PubMed for articles
Research Description Video
Department of Pathology and Laboratory Medicine
Cell and Molecular Biology Graduate Group
Education:
B.A. (Chemistry)
Lehigh University , 1988.
M.D.
Washington University, 1996.
Ph.D. (Neuroscience)
Washington University, 1996.
Certif. (Patient Oriented Research)
University of Pennsylvania, 2005.
Permanent linkB.A. (Chemistry)
Lehigh University , 1988.
M.D.
Washington University, 1996.
Ph.D. (Neuroscience)
Washington University, 1996.
Certif. (Patient Oriented Research)
University of Pennsylvania, 2005.
Description of Research Expertise
Research InterestsPlatelets, Platelet Factor 4, Atherosclerosis, Protein interactions, Murine models, Transcriptional regulation.
Key words: Platelets, Platelet Factor 4, Atherosclerosis, Protein interactions, Murine models, Tanscriptional regulation.
Description of Research
My laboratory is primarily interested in the biology and structure of platelet factor 4 (PF4). PF4 is a cationic protein found in the alpha-granules of platelets and is released upon platelet activation. It binds avidly to glycosaminoglycans on the surface of endothelial cells and is known to inhibit anti-thrombin III, resulting in increased clotting.
We are interested in the role of PF4 in several diseases, specifically atherosclerosis and heparin induced thrombocytopenia (HIT). We have found that PF4 is localized in atherosclerotic lesions and that the presence of PF4 correlated with pathological and clinical disease progression. Further, we have found that in vitro PF4 inhibits endocytosis of the LDL receptor, resulting in decreased LDL degradation and retention of LDL on the cell surface. Current studies are underway to further understand the cellular and molecular mechanisms responsible for this phenomenon and to examine the effects of PF4 on other lipoproteins and lipoprotein receptors. In vivo experiments are currently underway to further our understanding of these phenomena.
Another project in the lab is examining the molecular mechanisms of HIT. This rare but serious complication of heparin therapy is known to involve the recognition of PF4:heparin complexes by pathogenic auto-antibodies. It is also known that altering the ratio of heparin to PF4 alters the recognition of the complexes. Our working hypothesis is that the structure of the complexes formed at different heparin:PF4 ratios differs and that the structural changes are important for the expression of disease. We are investigating these structural changes and how these changes effect pathogenesis of HIT. Both in vitro and in vivo systems are being employed.
Rotation Projects for 2006-2007
PF4 activation of NF-kB and resulting pathobiology.
Structural mapping of monoclonal antibodies to platelet factor 4
Transcriptional effects of platelet specific chemokines
Murine models of atherosclerosis and lipoprotein metabolism
Lab personnel:
Ann Rux, PhD - Lab Manager
Tiffany Turrentine - Research Technician
Rachael Gordon – Undergraduate Student
Selected Publications
Sachais, B.S., Litvinov, R.I., Yarovoi, S.V., Rauova, L., Hinds, J.L., Rux, A.H., Arepally, G.M., Poncz, M., Cuker, A., Weisel, J.W., and Cines, D.B.: Dynamic antibody binding properties in the pathogenesis of HIT. Blood 120: 1137-1142, August 2012 Notes: PMID: 22577175 (Editorial Accompanying).Sachais, B.S., Rux. A.H, Cines, D.B., Yarovoi, S.V., Garner, L.I., Watson S.P., Hinds, J.L., Rux,J.J.: Rational design and characterization of platelet factor 4 antagonists for the study of heparin-induced thrombocytopenia. Blood 119(25): 5955-5962, June 2012 Notes: Plenary Paper. Inside Blood Accompanying.
Marshall, C.S., Andrzejewski, C., Carey, P.M., Crookston, K.P., Li, K., Lopez-Plaza, I., Sachais, B.S., Schwartz, J., Winters, J.L., Wong E.C.C, and Wu, Y.: Milestones for apheresis education. Journal of Clinical Apheresis Page: Epub Ahead of Print, June 2012.
Yvette C. Tanhehco, Ann H. Rux, and Bruce S. Sachais: Low Density Lipoprotein Apheresis Reduces PF4 on the Surface of Platelets: a Possible Protective Mechanism Against HITT. Transfusion 51: 1022-1029, October 2010 Notes: PMID: 20977482
Adamski, J., Jamensky, L., Ross, J., Siegel, D. L. Sachais, B. S.: Anaphylactoid-like reactions in a patient with HyperLp(a)lipidemia undergoing LDL apheresis with dextran sulfate adsorption and herbal therapy with the spice turmeric. Journal of Clinical Apheresis 25: 354-357, August 2010 Notes: PMID: 20806416
Roback, J.D.,Caldwell, S., Carson, J., Davenport, R., Drew, M.J., Eder, A., Fung, M., Hamilton, M., Hess, J.R., Luban, N., Perkins, J.G., Sachais, B.S., Shander, A., Silverman, T., Snyder, E., Tormey, C., Waters, J., and Djulbegovic, B.: Evidence-based practice guidelines for plasma transfusion. Transfusion 50: 1227-1239, June 2010 Notes: PMID: 20345562
Adamski, J.A., Carrutth Griffin, A., Eisenmann, C., Milone, M.C., Sachais, B.S.: Increased Risk of Citrate Reactions in Patients with Multiple Myeloma During Peripheral Blood Stem Cell Leukapheresis. Journal of Clinical Apheresis 25(4): 188-194, 2010 Notes: PMID: 20818713
Callan, M.B., Appleman, E.H., and Sachais, B.S.: Canine platelet transfusions. Journal of Veterinary Emergency and Critical Care 19(5): 401-415, October 2009 Notes: PMID: 19821881
Appleman, E.H., Sachais, B.S.,Patel, R., Drobatz, K.J., Groman, R.P., Kennedy, D.R., O'Donnell, P.A., Bryan, C., Callan, M.B. : Cryopreservation of canine platelets. Journal of Veterinary Internal Medicine 23: 138-145, February 2009 Notes: PMID: 19175732
Sachais, B.S., Turrentine, T., Dawicki-McKenna, J.M., Rux, A.H., Rader, D. and Kowalska, M.A. : Elimination of Platelet Factor 4 (PF4) from Platelets Reduces Atherosclerosis in C57Bl/6 and apoE-/- Mice. Thrombosis and Haemostasis 98: 1101-1113, November 2007 Notes: See Also Thromb Haemost 2007:95: 917-918 PMID: 18000617